Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

Samuel E. Jones, Jacqueline M. Lane, Andrew R. Wood, Vincent T. Hees, Jessica Tyrrell, Robin N. Beaumont, Aaron R. Jeffries, Hassan S. Dashti, Melvyn Hillsdon, Katherine S. Ruth, Marcus A. Tuke, Hanieh Yaghootkar, Seth A. Sharp, Yingjie Jie, William D. Thompson, Jamie W. Harrison, Amy Dawes, Enda M. Byrne, Henning Tiemeier, Karla V. Allebrandt, Jack Bowden, David W. Ray, Rachel M. Freathy, Anna Murray, Diego R. Mazzotti, Philip R. Gehrman, Debbie A. Lawlor, Timothy M. Frayling, Martin K. Rutter, David A. Hinds, Richa Saxena and Michael N. Weedon ()
Additional contact information
Samuel E. Jones: University of Exeter Medical School, Royal Devon & Exeter Hospital
Jacqueline M. Lane: Massachusetts General Hospital
Andrew R. Wood: University of Exeter Medical School, Royal Devon & Exeter Hospital
Vincent T. Hees: Netherlands eScience Center
Jessica Tyrrell: University of Exeter Medical School, Royal Devon & Exeter Hospital
Robin N. Beaumont: University of Exeter Medical School, Royal Devon & Exeter Hospital
Aaron R. Jeffries: University of Exeter Medical School, Royal Devon & Exeter Hospital
Hassan S. Dashti: Massachusetts General Hospital
Melvyn Hillsdon: University of Exeter
Katherine S. Ruth: University of Exeter Medical School, Royal Devon & Exeter Hospital
Marcus A. Tuke: University of Exeter Medical School, Royal Devon & Exeter Hospital
Hanieh Yaghootkar: University of Exeter Medical School, Royal Devon & Exeter Hospital
Seth A. Sharp: University of Exeter Medical School, Royal Devon & Exeter Hospital
Yingjie Jie: University of Exeter Medical School, Royal Devon & Exeter Hospital
William D. Thompson: University of Exeter Medical School, Royal Devon & Exeter Hospital
Jamie W. Harrison: University of Exeter Medical School, Royal Devon & Exeter Hospital
Amy Dawes: University of Exeter Medical School, Royal Devon & Exeter Hospital
Enda M. Byrne: Institute for Molecular Bioscience
Henning Tiemeier: Erasmus Medical Center
Karla V. Allebrandt: Industriepark Höchst
Jack Bowden: MRC Integrative Epidemiology Unit at the University of Bristol
David W. Ray: University of Manchester
Rachel M. Freathy: University of Exeter Medical School, Royal Devon & Exeter Hospital
Anna Murray: University of Exeter Medical School, Royal Devon & Exeter Hospital
Diego R. Mazzotti: University of Pennsylvania
Philip R. Gehrman: Perelman School of Medicine of the University of Pennsylvania
Debbie A. Lawlor: MRC Integrative Epidemiology Unit at the University of Bristol
Timothy M. Frayling: University of Exeter Medical School, Royal Devon & Exeter Hospital
Martin K. Rutter: University of Manchester
David A. Hinds: 23andMe Inc.
Richa Saxena: Massachusetts General Hospital
Michael N. Weedon: University of Exeter Medical School, Royal Devon & Exeter Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Being a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.

Date: 2019
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DOI: 10.1038/s41467-018-08259-7

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